N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazole carboxamide is generally known as Dasatinib and is represented by the following structural formula-1.

Dasatinib is a cyclic protein tyrosine kinase inhibitor indicated for newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase; adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib; and, adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy. It is also being evaluated for use in numerous other cancers, including advanced prostate cancer.
Dasatinib is approved in USFDA as SPRYCEL™ and is chemically mentioned in the label as N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl] amino]-5-thiazolecarboxamide, monohydrate compound of formula-1a.

It is a white to off-white powder, insoluble in water and slightly soluble in alcoholic solvents like ethanol and methanol.
U.S. Pat. No. 6,596,746 B1 (herein after. US'746) provided the first disclosure of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazole carboxamide, which also describes the process for preparing Dasatinib.
According to the basic patent US'746, dasatinib is prepared by reaction of the key intermediate of formula-2 with 1-(2-hydroxyethyl)piperazine in the presence of a base and a suitable solvent. A similar preparation method was later used in a number of other process patents, only varying the corresponding base or solvent. Through the selection of a suitable solvent or procedure a great number of solvates or polymorphs can be prepared. Polymorphs have been one of the most frequently studied physical characteristics of active pharmaceutical substances (API) recently. Thus, different polymorphs of one API may have entirely different physical-chemical properties such as solubility, melting point, mechanical resistance of crystals but they may also influence the chemical and physical stability. Then, these properties may have an impact on further processes such as handling of the particular API, grinding or formulation method. These various physical-chemical characteristics of polymorphs influence the resulting bioavailability of the solid dosage form. Therefore, looking for new polymorphs and solvates is becoming an important tool for obtaining a polymorph form with the desired physical-chemical characteristics.
U.S. Pat. No. 7,491,725 B2 (herein after US'725) describes the crystalline monohydrate, crystalline butanol solvate, crystalline ethanol solvate and anhydrous forms of Dasatinib (i.e., N-6 and T1H1-7). US '725 B2 also provides processes for the preparation of these mentioned forms of Dasatinib. Its continuation U.S. Pat. No. 8,242,270B2 also describes two ethanol solvates, i.e., hemi-ethanol and diethanol solvates.
PCT International Publication No WO2009053854A2 describes the preparation of a number of solvates or mixed solvates out of which especially the isopropanol, and mixed isopropanol/dimethyl sulfoxide solvates, as well as a new solid form B, another anhydrous polymorph of dasatinib, are worth mentioning.
PCT International Publication No WO2010067374A2 describes the preparation of other solvates/mixed solvates such as dimethyl formamide, isopropyl acetate, toluene, dimethyl sulfoxide and processes for the preparation.
API solvates or salts are used in drug formulations in many cases. In the case of solvates the limits for individual solvents, their contents or maximum daily doses have to be strictly observed. Then, these limits can dramatically restrict their effective use. Thus, the clearly most convenient option is the use of sufficiently stable polymorphs of API that do not contain any solvents bound in the crystalline structure.
Some of the above mentioned patent documents describe preparation of a stable anhydrous form (N-6) of dasatinib.
The discovery of new polymorphic form of a pharmaceutically useful compound provides a new opportunity to improve the performance characteristics of a pharmaceutical product.
The present inventors surprisingly found that the 1,2-propanediol solvate of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazole carboxamide, which is showing advantageous properties such as good solubility.
The present inventors surprisingly found that the stable and pure anhydrous form (N-6) and monohydrate form of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazole carboxamide via 1,2-propanediol solvate of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazole carboxamide, which is showing advantageous properties.